The goal of the research is a detailed description of the morphological and pharmacological organization of the rodent fastigial nucleus in both normal and lesioned animals. The specific aims of this proposal are to: 1) Analyze the fine structure of the fastigial nucleus utilizing electron microscopic and stereological techniques; 2) determine the morphology and distribution of angiotensin, renin, serotonin and noradrenalin immunoreactive cells and/or fibers in the fastigial nucleus; 3)determine the location and distribution of cholinergic, GABAnergic, adrenergic, serotonergic, glutamatergic, piperidinergic and angiotensin receptors in all four of the deep cerebellar nuclei but focusing on the fastigial nucleus; and 4) analyze the changes which occur in both receptor binding and functional activity in the cerebellum in general, and in the fastigial nucleus in particular, following lesions of either specific afferent fiber pathways to the cerebellum or specific precerebellar nuclei. The methods used to accomplish these aims will include electron microscopy, morphometric analysis, the combined Golgi-electron microscopic technique, immunohistochemistry, radiohistochemistry of neurotransmitter receptors, brain lesioning techniques and the 2-deoxy-glucose technique. As outlined, the proposed studies will provide important new information on the anatomical and neurochemical organization of the fastigial nucleus which will serve as a basis for future studies of this region. The data obtained from our lesion studies will provide valuable information which can be utilized in understanding the pharmacological and functional changes which occur in the human cerebellum following brain stem or cerebellar cortical lesions.